ES2583754T3 - Productos génicos expresados de manera diferencial en tumores y utilización de los mismos - Google Patents

Productos génicos expresados de manera diferencial en tumores y utilización de los mismos Download PDF

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ES2583754T3
ES2583754T3 ES11007329.3T ES11007329T ES2583754T3 ES 2583754 T3 ES2583754 T3 ES 2583754T3 ES 11007329 T ES11007329 T ES 11007329T ES 2583754 T3 ES2583754 T3 ES 2583754T3
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cells
tumor
antibody
associated antigen
tumors
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Ugur Sahin
Özlem TÜRECI
Michael Koslowski
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Ganymed Pharmaceuticals GmbH
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Ganymed Pharmaceuticals GmbH
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    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3076—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties
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Abstract

Anticuerpo, que se une específicamente a una proteína o a un polipéptido, que es codificado(a) por un ácido nucleico según SEC ID Nº: 7 u 8, para su utilización en un procedimiento diagnóstico o terapéutico, comprendiendo el procedimiento diagnóstico la administración del anticuerpo y estando el anticuerpo del procedimiento diagnóstico acoplado con un agente de diagnóstico.

Description

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tumores o a la parte del mismo.
En formas de realización adicionales, el antígeno asociado a tumores que debe detectarse o la parte del mismo está presente en un complejo con una molécula del CMH, en particular una molécula de HLA.
Una detección de un anticuerpo o la monitorización de la cantidad de anticuerpos puede tener lugar con una proteína o péptido, que se une específicamente al anticuerpo.
Una detección de células T citolíticas o células T cooperadoras o la monitorización de la cantidad de células T citolíticas o células T cooperadoras, que son específicas para complejos entre un antígeno o una parte del mismo y moléculas del CMH, puede tener lugar según la invención con una célula, que presenta el complejo entre el antígeno
o la parte del mismo y una molécula del CMH.
La sonda polinucleotídica utilizada para una detección o para una monitorización, el anticuerpo, la proteína o péptido
o la célula están, por ejemplo, marcados de manera detectable. En determinadas formas de realización el marcador detectable es un marcador radiactivo o un marcador enzimático. La detección de linfocitos T puede tener lugar adicionalmente mediante la detección de su proliferación, su producción de citocinas, así como su actividad citotóxica, que se desencadena mediante la estimulación específica con el complejo del CMH y antígeno asociado a tumores o partes del mismo. La detección de linfocitos T puede tener lugar además mediante una molécula del CMH recombinante o también un complejo de varias moléculas del CMH, que están cargadas con el respectivo fragmento inmunogénico de uno o varios de los antígenos asociados a tumores y mediante la puesta en contacto del receptor de células T específico, con lo que pueden identificarse linfocitos T específicos.
En un aspecto adicional se da a conocer un procedimiento para el tratamiento, el diagnóstico o la monitorización de una enfermedad, que se caracteriza por la expresión o expresión anómala de un antígeno asociado a tumores identificado según la invención, que comprende la administración de un anticuerpo, que se une al antígeno asociado a tumores o una parte del mismo y está acoplado con una sustancia o agente terapéutico o de diagnóstico. El anticuerpo puede ser un anticuerpo monoclonal. En formas de realización adicionales, el anticuerpo es un anticuerpo quimérico o humanizado o un fragmento de un anticuerpo natural.
La divulgación se refiere también a un procedimiento para el tratamiento de un paciente con una enfermedad, que se caracteriza por la expresión o expresión anómala de un antígeno asociado a tumores identificado según la invención, que comprende (i) tomar una muestra con células inmunorreactivas del paciente, (ii) poner en contacto la muestra con una célula huésped, que expresa el antígeno asociado a tumores o una parte del mismo, en condiciones que favorecen una producción de células T citolíticas frente al antígeno asociado a tumores o una parte del mismo, y (iii) introducir las células T citolíticas en el paciente en una cantidad, que es adecuada para lisar células que expresan el antígeno asociado a tumores o una parte del mismo. La divulgación se refiere igualmente a la clonación del receptor de células T de células T citolíticas frente al antígeno asociado a tumores. Este puede transferirse a otras células T, que de ese modo obtienen la especificidad deseada y pueden introducirse en el paciente tal como en el punto (iii).
En una forma de realización, la célula huésped expresa una molécula de HLA de manera endógena. En una forma de realización adicional, la célula huésped expresa una molécula de HLA y/o el antígeno asociado a tumores o la parte del mismo de manera recombinante. Preferentemente, la célula huésped no es proliferativa. En una forma de realización preferida, la célula huésped es una célula presentadora de antígeno, en particular una célula dendrítica, un monocito o un macrófago.
En un aspecto adicional se da a conocer un procedimiento para el tratamiento de un paciente con una enfermedad, que se caracteriza por la expresión o expresión anómala de un antígeno asociado a tumores, que comprende (i) la identificación de un ácido nucleico que codifica para un antígeno asociado a tumores identificado según la invención, expresado por células que están asociadas con la enfermedad, (ii) la transfección de una célula huésped con el ácido nucleico o una parte del mismo, (iii) el cultivo de la célula huésped transfectada para una expresión del ácido nucleico (esto no es obligatorio en el caso de alcanzar una tasa de transfección elevada), y (iv) la introducción de las células huésped o de un extracto de las mismas en el paciente en una cantidad, que es adecuada para aumentar la reacción inmunitaria contra las células del paciente, que están asociadas con la enfermedad. El procedimiento puede comprender además la identificación de una molécula del CMH, que presenta el antígeno asociado a tumores
o una parte del mismo, expresando la célula huésped la molécula del CMH identificada y presentando el antígeno asociado a tumores o una parte del mismo. La reacción inmunitaria puede comprender una reacción de células B o una reacción de células T. Por lo demás, una reacción de células T puede comprender la producción de células T citolíticas y/o células T cooperadoras, que son específicas para las células huésped, que presentan el antígeno asociado a tumores o una parte del mismo o son específicas para células del paciente, que expresan el antígeno asociado a tumores o una parte del mismo.
La divulgación se refiere también a un procedimiento para el tratamiento de una enfermedad, que se caracteriza por la expresión o expresión anómala de un antígeno asociado a tumores identificado según la invención, que comprende (i) la identificación de células del paciente, que expresan cantidades anómalas del antígeno asociado a
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